Genetic Risk Assessment of Type 2 Diabetes–Associated Polymorphisms in African Americans
| Autor: | Barry I. Freedman, Carl D. Langefeld, Jessica N. Cooke, S. Sandy An, Donald W. Bowden, Nicholette D. Palmer, Maggie C.Y. Ng, Jessica M. Hester |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male endocrine system Linkage disequilibrium Genotype endocrine system diseases Endocrinology Diabetes and Metabolism ADAMTS9 Protein 030209 endocrinology & metabolism Single-nucleotide polymorphism Type 2 diabetes Polymorphism Single Nucleotide Linkage Disequilibrium 03 medical and health sciences 0302 clinical medicine Internal Medicine Humans Medicine Genetic Predisposition to Disease Allele CDKAL1 Alleles Aged 030304 developmental biology Advanced and Specialized Nursing tRNA Methyltransferases 0303 health sciences Framingham Risk Score business.industry Membrane Proteins nutritional and metabolic diseases Cyclin-Dependent Kinase 5 Middle Aged medicine.disease Neoplasm Proteins Black or African American DNA-Binding Proteins ADAM Proteins Diabetes Mellitus Type 2 Commentary (See Cooke et al. p. 287) Commentary Female business Co-Repressor Proteins Transcription Factor 7-Like 2 Protein TCF7L2 Demography |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc11-0957 |
| Popis: | OBJECTIVE Multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2D) susceptibility have been identified in predominantly European-derived populations. These SNPs have not been extensively investigated for individual and cumulative effects on T2D risk in African Americans. RESEARCH DESIGN AND METHODS Seventeen index T2D risk variants were genotyped in 2,652 African American case subjects with T2D and 1,393 nondiabetic control subjects. Individual SNPs and cumulative risk allele loads were assessed for association with risk for T2D. Cumulative risk was assessed by counting risk alleles and evaluating the difference in cumulative risk scores between case subjects and control subjects. A second analysis weighted risk scores (ln [OR]) based on previously reported European-derived effect sizes. RESULTS Frequencies of risk alleles ranged from 8.6 to 99.9%. Eleven SNPs had ORs >1, and 5 from ADAMTS9, WFS1, CDKAL1, JAZF1, and TCF7L2 trended or had nominally significant evidence of T2D association (P < 0.05). Individuals carried between 13 and 29 risk alleles. Association was observed between T2D and increase in risk allele load (unweighted OR 1.04 [95% CI 1.01–1.08], P = 0.010; weighted 1.06 [1.03–1.10], P = 8.10 × 10−5). When TCF7L2 SNP rs7903146 was included as a covariate, the risk score was no longer associated with T2D in either model (unweighted 1.02 [0.98–1.05], P = 0.33; weighted 1.02 [0.98–1.06], P = 0.40). CONCLUSIONS The trend of increase in risk for T2D with increasing risk allele load is similar to observations in European-derived populations; however, these analyses indicate that T2D genetic risk is primarily mediated through the effect of TCF7L2 in African Americans. |
| Databáze: | OpenAIRE |
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